The human polyomavirus, JC virus, is the etiologic agent of the central nervous system (CNS) demyelinating disease progressive multifocal leukoencephalopathy (PML), a relatively rare disease typically affecting immune compromised patients, though other patients can also be affected. JC virus infection is globally ubiquitous with more than half the population having been exposed. Approximately 30% of exposed individuals will become latently infected in kidney uroepithelial cells, excreting high viral DNA copy numbers into the urine without evidence of any pathologic consequence in any tissues including the brain. Despite the high infection rate, a small minority of healthy subjects with JC virus infection develop PML.
The incidence of PML is highest in HIV-1 infected individuals and is an AIDS defining illness (approximating 3/100 AIDS patients have PML). Further, the incidence of PML is 1/90 in patients with multiple sclerosis (MS) who are treated with more than 24 doses of the monoclonal antibody directed to α4 integrins, natalizumab, and have history of immune suppressive therapy.
Certain JC virus variants are known to have a greater association with PML. For example “Prototype” JC virus is far more pathogenic than “Archetype” JC virus. Known assays to detect the presence of JC virus in a biological sample and distinguish between Archetype and Prototype JC virus are complex, and require a DNA sequencing step to distinguish between Archetype and Prototype JC virus. Thus, there is a need for a simple assay to distinguish JC virus variants (such as Prototype and Archetype variants) in a biological sample, that does not require DNA sequencing, in order to determine if an individual is at increased risk for, or has, PML.